Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer

Objective:A randomized multicenter (14 centers) trial was conducted in 114 men with prostate cancer to determine whether the antiestrogen tamoxifen (‘Nolvadex’) 20 mg or the aromatase inhibitor anastrozole (‘Arimidex’) 1 mg prevent gynecomastia and breast pain during treatment with the non-steroidal antiandrogen bicalutamide (‘Casodex’) 150 mg, without compromising efficacy, safety, or quality of life. Plasma samples were collected in a subgroup of these patients to investigate whether trough (pre-dose) concentrations of bicalutamide 150 mg are influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg; the results of this pilot study are reported in this article. Methods: A subpopulation of patients from a randomized placebo-controlled trial evaluating tamoxifen 20 mg and anastrozole 1 mg for the prevention of gynecomastia and breast pain in men receiving bicalutamide 150 mg for early or recurrent prostate cancer were selected on a voluntary basis from three of the trial centers. Plasma samples were collected on days 7, 14, 28, and 84 of therapy and analyzed to determine the plasma concentrations of (R)–bicalutamide and (S)-bicalutamide. In addition, plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were determined. Results: A total of 21 patients were selected. There was no significant difference between treatment groups with respect to the trough plasma concentrations of either bicalutamide enantiomer at any point during the study. Plasma concentrations of the enantiomers, and the relative proportion of the ®)- and (S)–enantiomers, were consistent with those reported in previous studies. Plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were also similar to those described elsewhere in the literature. Conclusions: The findings of this pilot study suggest that trough plasma concentrations of bicalutamide enantiomers following administration of bicalutamide 150 mg are not markedly influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg. However, an effect of tamoxifen on bicalutamide pharmacokinetics can not be completely excluded due to the size of this study. Further studies are needed to clarify the effect of tamoxifen on bicalutamide pharmacokinetics and prostate cancer control in bicalutamide-treated patients. ‘Arimidex’, ‘Casodex’, and ‘Nolvadex’ are trademarks of the AstraZeneca group of companies